Evidence map›Paper›PMID 34524848›Full record

ArticleScience advances2021

Parallel characterization of cis-regulatory elements for multiple genes using CRISPRpath.

Xingjie Ren, Mengchi Wang, Bingkun Li, Kirsty Jamieson, Lina Zheng, Ian R Jones, Bin Li, Maya Asami Takagi, Jerry Lee, Lenka Maliskova and 11 more

Abstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Xingjie RenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2348-4162
Mengchi WangBioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Bingkun LiInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-6822-9440
Kirsty JamiesonInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3110-7081
Lina ZhengBioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Ian R JonesInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Bin LiLudwig Institute for Cancer Research, La Jolla, CA, USA.ORCID 0000-0003-2734-6418
Maya Asami TakagiInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Jerry LeeInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8626-3594
Lenka MaliskovaInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7677-3833
Tsz Wai TamInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Miao YuLudwig Institute for Cancer Research, La Jolla, CA, USA.
Rong HuLudwig Institute for Cancer Research, La Jolla, CA, USA.ORCID 0000-0002-0660-0387
Lindsay LeeDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Armen AbnousiDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Gang LiDepartment of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0003-0759-9063
Yun LiDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0002-9275-4189
Ming HuDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.ORCID 0000-0003-0987-2916
Bing RenLudwig Institute for Cancer Research, La Jolla, CA, USA.ORCID 0000-0002-5435-1127
Wei WangBioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0003-4377-5060
Yin ShenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9901-5613

Funding

San Diego Center for 4D Nucleome ResearchU54DK107977 · NIDDK · LUDWIG INSTITUTE FOR CANCER RES LTD · PI REN, BING · 2015 to 2019
$9.4M
High throughput CRISPR-mediated functional validation of regulatory elementsUM1HG009402 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REN, BING, SHEN, YIN · 2017 to 2021
$8.4M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
NHGRI NIH HHS UM1 HG009402NIDDK NIH HHS U54 DK107977NIGMS NIH HHS T32 GM007175
6 · The paper itself

Abstract

Current pooled CRISPR screens for cis-regulatory elements (CREs), based on transcriptional output changes, are typically limited to characterizing CREs of only one gene. Here, we describe CRISPRpath, a scalable screening strategy for parallelly characterizing CREs of genes linked to the same biological pathway and converging phenotypes. We demonstrate the ability of CRISPRpath for simultaneously identifying functional enhancers of six genes in the 6-thioguanine–induced DNA mismatch repair pathway using both CRISPR interference (CRISPRi) and CRISPR nuclease (CRISPRn) approaches. Sixty percent of the identified enhancers are known promoters with distinct epigenomic features compared to other active promoters, including increased chromatin accessibility and interactivity. Furthermore, by imposing different levels of selection pressure, CRISPRpath can distinguish enhancers exerting strong impact on gene expression from those exerting weak impact. Our results offer a nuanced view of cis-regulation and demonstrate that CRISPRpath can be leveraged for understanding the complex gene regulatory program beyond transcriptional output at scale.

Identifiers

PMID34524848
PMCPMC8443183

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.